BACKGROUND: The international Inherited Neuropathy
Consortium (INC) was created with the goal of obtaining
much needed natural history data for patients with
Charcot-Marie-Tooth (CMT) disease. We analysed clinical
and genetic data from patients in the INC to determine
the distribution of CMT subtypes and the clinical
impairment associated with them.
METHODS: We analysed data from 1652 patients
evaluated at 13 INC centres. The distribution of CMT
subtypes and pathogenic genetic mutations were
determined. The disease burden of all the mutations was
assessed by the CMT Neuropathy Score (CMTNS) and
CMT Examination Score (CMTES).
RESULTS: 997 of the 1652 patients (60.4%) received
a genetic diagnosis. The most common CMT subtypes
were CMT1A/PMP22 duplication, CMT1X/GJB1
mutation, CMT2A/MFN2 mutation, CMT1B/MPZ
mutation, and hereditary neuropathy with liability to
pressure palsy/PMP22 deletion. These five subtypes of
CMT accounted for 89.2% of all genetically confirmed
mutations. Mean CMTNS for some but not all subtypes
were similar to those previously reported.
CONCLUSIONS: Our findings confirm that large numbers
of patients with a representative variety of CMT subtypes
have been enrolled and that the frequency of achieving
a molecular diagnosis and distribution of the CMT
subtypes reflects those previously reported. Measures of
severity are similar, though not identical, to results from
smaller series. This study confirms that it is possible to
assess patients in a uniform way between international
centres, which is critical for the planned natural history
study and future clinical trials. These data will provide a
representative baseline for longitudinal studies of CMT.
CLINICAL TRIAL REGISTRATION ID NUMBER: NCT0119307
